IGF has the longer half life; therefore it's used as a screening test for acromegaly. GH has a short halflife so it's not the first test in screening.

IGF-1 is elevated in insulin resistance.

Gross anatomy


Micro anatomy

[[Encodrinology MCQ discussion#Growth Hormone disorder diagnosis and investigation]]

Stimulation: GHRH, Ghrelin
GH secretion peaks in early puberty

• Peak GH secretory activity occurs within an hour after the onset of deep sleep.
• Exercise
• trauma and sepsis (it's a stress hormone)

[!Tip] Mnemonic: GH affects all macromolecules - makes things grow

• Lipids -> increase lipolysis
• Proteins -> Increased protein synthesis
• Electrolytes -> Phosphate, salt and water retention
• Bone -> Epiphyseal bone growth
  [[Encodrinology MCQ discussion#Growth Hormone disorder diagnosis and investigation|Diagnosis and Investigation of GH disorders]]

Acromegaly

Associated features and pathologic basis

As commonest cause if somatotroph adenoma:
acreomegaly is associated with symptoms caused by pressure effect of adenoma:

1. Headache, bitemporal hemianopia, cranial nerve defects
2. Decreased secretion of other pituitary hormones -> most commonly gonadotrophins
   1. Menstrual dysfunction, vaginal atrophy, galactrorrhea
3. Hyperprolactinaemia - either increased [[#Prolactin]] secretion from the somatotroph adenoma or inhbition of dopaminergic inhibition
4. Effects of GH and IGF-1 Excess:
   1. Soft tissue overgrowth - large tongue, carpal tunnel syndrome + the other classic ones
   2. Joints - Hypertrophic arthorpathy, back pain, kyphosis, hypogonadism induced osteoporosis
   3. Visceral organ enlargement - thyroid, heart, liver, lungs
      1. heart: cardiomyopathy and LVH with diastolic dysfunction and arrhythmias - secondary to hypertension
      2. Hypertension: GH-IGF-I excess -> enhanced sodium- and water retention -> expansion of plasma volume and increased systemic vascular resistance. Source
         3. Hyperinsulinaemia may also stimulate salt and water retention Source
   4. Metabolic - insulin resistance and DM
   5. Sleep apnea
   6. colonic neoplasms

Level of secretion of prolantin due to a given stimulus proportional to background hyperplasia of lactotrophs which is driven by oestrogen.
Prolactin secretion by lactotrophs is under tonic inhibition of dopamine (which acts on D2 receptors of the lactotrophs) secreted by the tuberoinfundibular pathway, originating in the arcuate nucleus of the hypothalamus.

Hyperprolactinaemia causes amenorrhoea
StatPearls prolactin

#2023BSQ Q3

#2023GM Q28

Summary of Parkinson's pathology

Polygenic inheritance pattern - genes but possible env factor interact to produce Parkinson's disease.
Parkinson's disease ≠ Parkinsonian syndromes.
Pathogensis: Loss of dopaminergic neurons in past compacta of substantia nigra of midbrain which project to the striatum of the basal ganglia. 70% loss has occured when symptoms appear.
Pathology: Lewy bodies (neuronal inclusions) seen
Symptoms Usually more prominent on one side.

Histologic changes in chronic and acute hepatitis

Regulation of gastric acid secretion

#2023BSQ Q37

Secreted by parietal cells under regulation of

1. encocrine - Gastrin
   1. Gastrin is the major endocrine regulator of the secretory response.
   2. Secreted in reponse to gastric distention and amino acids (and vagal stimulation)
   3. Gastrin from G cells in the antrum of the pylorus stimulates histamine release from ECL cells -> histamine stimulates acid secretion from parietal cells
   4. Gastrin is also a trophic upregulator of parieral cell mass.
2. paracrine - Histamine and somatostatin
   1. Somatostatin - potent anti acid hormone. Secreted by D cells located throughout gastric mucosa and from oxyntic glands. It inhibits histamine release -> reduces parietal cell acid production.
   2. Histamine - Secreted from ECL cells, localized to the acid-secreting oxyntic or body mucosa, in direct proximity to the parietal cell. Binds H2 receptor and promotes acid secretion.
3. autocrine -
   1. Prostaglandins - PGE2 and PGI2 produced by marophages and capillary endothelium in the gastric mucosa are [[General Pharmacology#Prostaglandin and COX pathway|autocrine factors that inhibit ]]
      1. acid secretion,
      2. histamine-stimulated parietal cell function,
      3. and gastrin-stimulated histamine release
4. neural - acetylcholine
   1. ACh
      1. stimulates parietal cell acid secretion,
      2. gastrin release and
      3. inhibits somatostatin.

Functions of gastric acid:

1. Helps in absorption of (FeCaB)
   1. Iron
   2. Calcium
   3. Vitamin B12
2. Prevents intestinal infections

3 phases of secretion

1. Cephalic - ACh
2. Gastric - Gastrin
3. Intestinal - mediators unknown

Fundus and body have gastric glands which have chief cells at their bases. Chief cells secrete pepsinogen which gets activated to pepsin in the low pH (<4) environment of the stomach. (Chief cells also produce gastric lipase)

Paraproteinemias

[!INFO] Definition of a Paraprotein
Very high levels of a single immunoglobulin is called a paraprotein or M protein (M for monoclonal). Caused by monoclonal proliferation of plasma cells

The cause for the plasma cell proliferation could be

1. Non malignant - but still dangerous because of paraprotein effects
2. Premalignant
   1. Small clone of premalignant cells produces M protein with no symptoms => MGUS
3. Malignant

Most premalignant disorders in medicine have limited clinical consequence until malignant transformation occurs. In contrast, premalignant clonal expansion of plasma cells can result in disabling or fatal disease related to the secreted immunoglobulin, termed monoclonal gammopathy of clinical significance

The paraprotein can consist of

1. Heavy and light chain (intact Ig)
2. Heavy chains only
3. Light chains only - when free kappa or lambda light chains appear in the urine -> bence jones proteins

Clinical manifestations of paraproteinemias

• agglutination of RBCs - Cold agglutinin disease
• Insolubility in low temperatures - Cryoglobulinemia
• Increased viscocity - Waldenström macroglobulinemia
• Deposition in tissues - AL Amyloidosis
• Kidney impairement -
• Neuropathy - POEMS Syndrome

Many causes: See UpToDate table "Disorders associated with the presence of a monoclonal gammopathy"

Waldenstrom Macroglobinaemia

(Youtube) -
aka Lymphoplasmacytic lymphoma

blood cancer affecting B lymphocytes.
Commoner in males > 50 years old. MYD88 gene mutation + CXCR4 gene (these are not inherited defects)
High numbers in bone marrow ->high IgM -> Blood becomes extremely thick.
IgM is the largest of the antibody types -> "macroglobin"
Signs and Symptoms : damage to small blood vessels - nose and gums.
Retina can be involved - impaired vision.
RBC crowded out of bone marrow -> anaemia
Tingling in exremeties
Ig accumulates in LN, spleen, liver. -> hepatosplenomegaly
If asymptomatic -> watchful waiting
If thick block -> plasmapheresis
Rituximab + other agents